• Animal cells and systems
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• v.5 no.2
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• pp.139-143
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• 2001

Alzheimer's disease is the most common form of dementia and no cure is known so far. Extensive genetic works and in vitro experiments combined with clinical observations link amyloid $\beta$--protein (A$\beta$-) to the pathogenesis of Alzheimer's disease (AD). It was hypothesized that $A\beta$- becomes toxic when it adopts a fibrillar conformation. Recently, non-fibrillar form of $A\beta$- was observed and the potential role in the pathogenesis of AD became an interesting subject. In this study, the cytotoxicity of non-fibrillar $A\beta$- and fibrillar $A\beta$- was compared on oxidative stress, membrane damage, or nucleosome break down. Non-fibrillar $A\beta$- was not toxic in peripheral nervous system-derived cells but significantly toxic in central nervous system-derived cells while fibrillar $A\beta$- was non-selectively toxic in both cell culture. The neurotoxicity of non-fibrillar $A\beta$- was reproduced in semi-in vivo culture of mouse brain slice. In conclusion, non-fibrillar $A\beta$- could be more relevant to the selective neurodegeneration in Alzheimer's brains than fibrillar $A\beta$- and further research needs to be done for identification of the cause of AD.

• Journal of the Korean Society of Food Culture
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• v.35 no.6
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• pp.605-612
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• 2020

In this study, 11 plant extracts from Bangladesh were used to evaluate the total phenolic and flavonoid content, in vitro antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzthiazolin-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assay. Also, the inhibitory effect of nitric oxide (NO) production in RAW 264.7 macrophage cell line and the neuroprotective effect on H2O2-induced PC12 cells were tested. Our results revealed that Piper betle L. showed the highest total phenolic content (162.2 mg GAE/g extract) among the 11 plants from Bangladesh. Most plants showed strong radical scavenging effects and ferric reducing antioxidant power. Besides, Piper betle L. protected PC12 neuronal cells against H2O2 related oxidative stress in LPS-induced PC12 cells. Regarding the anti-inflammatory effect, Piper betle L. significantly inhibited NO accumulation in LPS-induced RAW 264.7 cells. Our results provide evidence that Piper betle L. could be useful for the development of functional health foods.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.12-21
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• 2018

Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from Photorhabdus are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (5), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, $75{\mu}M$ 3 significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, $Ca^{2+}$ influx, and lipid peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-${\gamma}$-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-${\alpha}$. Anthraquinones 3 and 4 derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound 5 is reported for the first time in this study.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.835-845
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• 2008

Objectives : The purpose of this study was to investigate the effect of FS for the modulation of ROS and MMP in a hypoxic model of cultured rat cortical cells. Methods : For the effect of FS on the viability, FS was added to culture media (neurobasal supplemented with B27) and cell viability was measured by LDH assay. To investigate the effects of FS on ROS generation and MMP preservation, cells grown in FS-containing media were given a hypoxic shock(2% $O_2/5%$ $CO_2$, $37^{\circ}C$, 3 hrs) on DIV 10, stained with $H_2DCF-DA$(10 nM) and JC-1, respectively, and observed by fluorescent microscope. Results : 1. FS has a protective effect of cortical cells in both normoxia and hypoxia. 2. FS reduced the generation of ROS and this reduction was especially significant at 3 days after hypoxia. 3. FS was effective for the maintenance of MMP in hypoxia, and this efficacy was especially significant at 3 days after hypoxia. Conclusions : Taken together, these results indicate that FS attenuates ROS generation and MMP dissipation, which eventually protects from neuronal cell death in hypoxia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1111-1119
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• 2004

In this study, we investigated that the effects of corynoxeine on the apoptosis by inducible CT105 in PC 12 cells and neuronpathogenic agent as CT105 confirmed with apoptosis, DNA fragmentation, neurite outgrowth and immunocytochemistry analysis This study examines whether corynoxeine have an anti-alzhmeimer agent by inhibition of apoptosis by CT105 and induces neurite outgrowth. Cytotoxicity was assessed in PC12 cell cultures by DNA fragmentation and measuring lactate dehydrogenase (LDH) in the culture media. The treatment of corynoxeine in exposure of cultures to CT105 and provided complete protection against cytotoxicity. CT105-induced cytotoxicity was blocked by apoptotsis, repaired by DNA fragmentation, neurite outgrowth and exposure to CT105 expression and regenerated with neurite outgrowth and immunocytochemistry by corynoxeine. These results indicate that in neuronal cell cultures, damage of T105, repaired excitotoxicity by corynoxeine and CT105-induced cytotoxicity is blocked primarily by the activation of anti-apoptosis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.123-135
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• 2006

Alzheimer's disease (AD) is the most common form of dementia in the aging population and is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques - extracellular insoluble, congophilic protein aggregates composed of amyloid $\beta$ (A$\beta$) and neurofibrillary tangles (NFTs) - inyracellular lesions consisting of paired helical filaments from hyperphosphorylated cytoskeletal tau protein as described by Alois Alzheimer a century ago. These hallmarks still serve as the major criteria for a definite diagnosis of the disease. Consequently, one of the key strategy for drug development in this disease area focuses on reducing the concentration of cerebral A$\beta$ plaque by using substances that inhibit A$\beta$ fibril formation. We focused on developing inhibitors by synthesizing several kinds of aromatic molecules. The synthetic compounds were initially screened to evaluate the effective compound by tioflavin T fluorescence assay. The selected effective compounds were tested cytotoxicity and protective effect from A$\beta$-induced neuronal toxicity by cell based MTT assay with HT22 hippocampal neurons. The BBB permeability on effectors was also tested in in vitro co-culture model(HUVEC/C6 cell line). The behavior test wea carried out in mutant APP/PS1 transgenic mouse model of Alzheimer's disease. And inhibition of A$\beta$ fibril formation by the effective compound was monitored with transmitted electron microscopic images.

• Journal of Life Science
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• v.14 no.2
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• pp.291-295
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• 2004

Rooibos (Aspalathus linearis) (RB) is a leguminous shrub native to the mountainous areas of the northwestern Cape Province in South Africa. RB tea infusions are the fermentation products of its leaves and fine sterns, and known to have a high antioxidative activity due to the presence of flavonoids and phenolic acids. We investigated the effects of RB tea on the alleviation of oxidative stress on cultured rat cortical neurons in a hypoxic model. Measurement of lactate dehydrogenase (LDH) released into culture media revealed that RB increased cell viabilities in both normoxia (6-18%) and hypoxia (2-24%) dose-dependently (10-100 $\mu\textrm{g}$/ml) on 16 days in vitro (3 days after treatment). Visualization of cell morphology by expression of GFP-Hsc70 fusion protein showed that RB (50 $\mu\textrm{g}$/ml) reduced the average vacuolated soma from 55.4$\pm$4.59% (no RB addition) to 40.9$\pm$6.3% (RB addition) on 5 days after hypoxia. Our results proves efficacy of RB in the neuroprotection of hypoxic neurons and extend application for RB into the prevention and/or treatment of neuronal damages.

• Korean Journal of Veterinary Service
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• v.19 no.1
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• pp.1-29
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• 1996

This study was conducted to elucidate the pathogenesis of Aujeszky's disease virus(ADV) by histopathologic examination. The first Korean ADV Isolate, which was isolated from piglets with clinical signs of Aujeszky's disease in Yangsan(YS) county, Kyungnam province, was inoculated into 32 days old piglets with a dose of $10^{5.9}$$TCID_{50}/ml$ through intranasal or intramuscular route. These piglets were sacrificed at intervals of every 24hrs for 8 days. The virulence of YS strain was determined by the observation of clinical signs, gross findings, and histopathologic changes in tissues. The virus recovery test was performed from brain, spleen, lung and tonsil in cell culture. The pathogenesis of YS strain was determined by the observation of histopathologlc lesions in CNS and neuronal tracts. The major clinical signs were fever, anorexia, dyspnea, constipation, tremor, ataxia, circling movement, hindleg paralysis and salivation. The clinical signs were more severe in piglets of the group inoculated intranasally than those of the intramuscularly inoculated gorup. Lymphocytopenia was detected on day 5 to day 6 postinoculation (PI). The ADV was recovered from the tissue homogenates of tonsil, lung, spleen and cerebrum in cell culture. The highest virus titer was detected from tonsil between day 6 and day 7 PI. Reddish sublobar consolidation foci were scattered in the apical and cardiac lobes of lung. Although yellowish necrotic foci were detected in tonsil and liver, hemorrhagic lesions were mainly observed in heart, kidney and lymph nodes. Histopathologically, degeneration and necrosis of nerve cells, nonsuppurative meningoe-ncephalitis, nodular gliosis and perivascular cuffings were observed in CNS. Multifocal fibronecrotic foci were observed in lung, liver, lymph nodes and spleen. The major pathologic changes were detected in the midbrain, pons and medulla oblongata. Eosinophilic intranuclear inclusion bodies were mainly observed in epithelia and /or macrophages of tonsil, liver, lung, spleen and submandibular lymph nodes, and neurons of brain, respectively. Observation of viral particles at various stages of replication were possible from the endothelial cells of the alveolar capillaries and tonsillar crypt epithelia by transmission electron microscope.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.159-174
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• 2007

Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one's biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides $(Rb_1$ Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

• Journal of Embryo Transfer
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• v.32 no.2
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• pp.39-45
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• 2017

Mesenchymal stem cells (MSCs) have been considered an alternative source of neuronal lineage cells, which are difficult to isolate from brain and expand in vitro. Previous studies have reported that MSCs expressing Nestin ($Nestin^+$ MSCs), a neuronal stem/progenitor cell marker, exhibit increased transcriptional levels of neural development-related genes, indicating that $Nestin^+$ MSCs may exert potential with neurogenic differentiation. Accordingly, we investigated the effects of the presence of $Nestin^+$ MSCs in bone-marrow-derived primary cells (BMPCs) on enhanced neurogenic differentiation of BMPCs by identifying the presence of $Nestin^+$ MSCs in uncultured and cultured BMPCs. The percentage of $Nestin^+$ MSCs in BMPCs was measured per passage by double staining with Nestin and CD90, an MSC marker. The efficiency of neurogenic differentiation was compared among passages, revealing the highest and lowest yields of $Nestin^+$ MSCs. The presence of $Nestin^+$ MSCs was identified in BMPCs before in vitro culture, and the highest and lowest percentages of $Nestin^+$ MSCs in BMPCs was observed at the third (P3) and fifth passages (P5). Moreover, significantly the higher efficiency of differentiation into neurons, oligodendrocyte precursor cells and astrocytes was detected in BMPCs at P3, compared with P5. In conclusion, these results demonstrate that neurogenic differentiation can be enhanced by increasing the proportion of $Nestin^+$ MSCs in cultured BMPCs.